COAGULATION STUDIES WITH LINEAR COPOLYMERS OF ALIPHATIC HYDROCARBONS AND MALEIC ACID - NEW CLASS OF ANTICOAGULANTS

1. 1. Polymers of ethylene maleic acid (EMA) and its divinyl ether congener (Pyran) have anticoagulant effects in fibrinogen clotting by thrombin. Measurements of clotting time, clot opacity, yield and structure indicate that different effects are produced at distinctly different and broad concentration ranges of polymer. Fibrinogen clotting is exquisitely sensitive to EMA over a low range (less than 1 EMA:400 fibrinogen, w/w), about 4 times more than to heparin. Pyran equals EMA in potency. 2. 2. Antithrombic action in this range is referable to progressive fibrin monomer formation; co-presence of 0.25-1.0 μg polymer with 0.5 mg fibrin monomer removes approx. 40 thrombin units. Antithrombic capacity is proportional to thrombin concentration, the latter determining speed and quantity of fibrin monomer formation. Anticoagulant activity is less with relatively low-molecular-weight material. 3. 3. At progressively higher polymer concentration ranges anticoagulant activity diminishes, returning almost to normal, and again becoming prominent as concentration is increased. Here polymerization is only retarded; ultimate clot yield is unaffected. Clot structure, on the other hand, is compromised over all concentration ranges. 4. 4. These polymers share many properties of heparin and heparinoids. The EMA and Pyran data suggest that the antithrombic action of heparin in the purified fibrinogen-thrombin system, still controversial, is via the same mechanism. 5. 5. The biological significance of the findings and their possible application to the problem of blood-compatible surfaces is discussed. © 1969.